Enzyme-induced mineralization of hydrogels with amorphous calcium carbonate for fast synthesis of ultrastiff, strong and tough organic–inorganic double networks

Abstract

Hydrogels with good mechanical properties have great importance in biological and medical applications. Double-network (DN) hydrogels were found to be very tough materials. If one of the two network phases is an inorganic material, the DN hydrogels also become very stiff without losing their toughness. So far, the only example of such an organic–inorganic DN hydrogel is based on calcium phosphate, which takes about a week to be formed as an amorphous inorganic phase by enzyme-induced mineralization. An alternative organic–inorganic DN hydrogel, based on amorphous CaCO3, which can be formed as inorganic phase within hours, was designed in this study. The precipitation of CaCO3 within a hydrogel was induced by urease and a urea/CaCl2 calcification medium. The amorphous character of the CaCO3 was retained by using the previously reported crystallization inhibiting effects of N-(phosphonomethyl)glycine (PMGly). The connection between organic and inorganic phases via reversible bonds was realized by the introduction of ionic groups. The best results were obtained by copolymerization of acrylamide (AAm) and sodium acrylate (SA), which led to water-swollen organic–inorganic DN hydrogels with a high Young’s modulus (455 ± 80 MPa), remarkable tensile strength (3.4 ± 0.7 MPa) and fracture toughness (1.1 ± 0.2 kJ m−2). Graphical Abstract The present manuscript describes the method of enzymatic mineralization of hydrogels for the production of ultrastiff and strong composite hydrogels. By forming a double-network structure based on an organic and an inorganic phase, it is possible to improve the mechanical properties of a hydrogel, such as stiffness and strength, by several orders of magnitude. The key to this is the formation of a percolating, amorphous inorganic phase, which is achieved by inhibiting crystallization of precipitated amorphous CaCO3 with N-(phosphonomethyl)glycine and controlling the nanostructure with co polymerized sodium acrylate. This creates ultrastiff, strong and tough organic–inorganic double-network hydrogels.

Reinforcing hydrogels with in situ formed amorphous CaCO3

“…These results suggest that the percolating ACC structure that we observe under this condition contributes to the increased stiffness of the hydrogel, in good agreement with recent reports on the hydrogel reinforcement with amorphous calcium phosphate (ACP) nanoparticles [11] and ACC nanoparticles. [41] Similarly, the critical extension for crack initiation in hydrogels mineralized with a Mg/Ca ratio of 5/1 is much higher than that measured for all the other samples, as shown in the force-extension curves in Figure 3f and S11. The chemical interactions between the minerals and the hydrogel are independent of the Mg/Ca ratio, as shown in Figure S8.…”

Improving the Strength of Ultrastiff Organic–Inorganic Double-Network Hydrogels

“…Analytical investigation of the mineralized hydrogel was carried out analogous to previous publications. − ,, The freeze-dried, mineralized composite networks were broken in liquid nitrogen prior to further analysis. The cross-sections were investigated by scanning electron microscopy (SEM).…”

“…Exchanging one of the organic networks in a DN hydrogel with an inorganic network can significantly improve the mechanical properties in terms of stiffness. − While various methods are known to implement inorganic materials to hydrogels, ,− the highest improvement in stiffness has been achieved by forming a percolated inorganic phase within the hydrogel network, which is done by the enzymatic mineralization of hydrogels with calcium phosphate induced by alkaline phosphatase (AP) and more recently with amorphous calcium carbonate catalyzed by urease . These methods yield a percolating organic–inorganic DN hydrogel with Young’s moduli of up to 440 MPa.…”

“…42−44 While various methods are known to implement inorganic materials to hydrogels, 40,44−56 the highest improvement in stiffness has been achieved by forming a percolated inorganic phase within the hydrogel network, 44 which is done by the enzymatic mineralization of hydrogels with calcium phosphate induced by alkaline phosphatase (AP) and more recently with amorphous calcium carbonate catalyzed by urease. 57 These methods yield a percolating organic−inorganic DN hydrogel with Young's moduli of up to 440 MPa. However, the great improvement of stiffness is accompanied by a rather low strength, (∼1−3 MPa).…”

Enzyme‐Induced Ferrification of Hydrogels for Toughening of Functional Inorganic Compounds

“…Another important influencing factor for tough organic/inorganic hydrogels is to find the percolation point of the inorganic matrix, because beyond this point the inorganic phase renders the material brittle as well. [ 43 , 46 ] Thus, a PDMA‐ l ‐TEG network with 1 wt% urease was ferrified at 20 and 60 °C, respectively, and samples were taken at regular intervals and examined optically and by SEM, as well as thermogravimetrically.…”